The principal aim of the research program set forth in this application is to improve the synthetic methodology currently used to synthesize compounds with anticancer activity. In particular the stereoselectivity of the synthetic reactions is of major concern. Some examples of active compounds are the terpenoids; phyllanthoside, which has demonstrated activity against the NCI murine B16 melanoma as well as some life extension against the PS leukemia cell line, and taxol, which has demonstrated activity against the B16 melanoma as well as the colon CX-1 adenocarcinoma xenograft and the MX-1 mammary carcinoma xenograft. While the source of these compounds is from plant extracts, a suitable synthetic route would be preferable| The work outlined herein will greatly assist with the ongoing development of synthetic routes to the compounds mentioned above as well as offer the possibility for improvement in the synthetic routes to the tetracyclane antitumor antibiotics in the daunomycin family and the novel spirocyclic antitumor compound fredericamycin. The overall, long range goal of this work remains to explain the reactivity of the most common and useful organic nucleophiles and to predict with certainty the stereochemistry of the important synthetic reactions in which these species are used. The substrates under study are the primary reagents in the construction of architecturally complex organic molecules such as the terpenoid tumor promoters and inhibitors and especially the macrolide antibiotics. Positive results from this investigation will permit a more rational choice of reagents for the asymmetric synthesis of the physiologically active organic molecules.